François Boucher MD, FRCPC Community acquired pneumonia (CAP): Why is this still a problem?

Objectives After this presentation, participants will be able to: Determine appropriate agents, routes and duration of treatment. Recognize how local epidemiology influences treatment choices. Manage complications of CAP.

Emergent problems in pediatric community-acquired pneumonia Severe pneumonia Pulmonary abscess formation: GAS Pulmonary necrosis & fibrosis: MRSA Pneumatocoeles: S. aureus Resistant organisms: S. pneumoniae 19A Parapneumonic effusion Increasing incidence Difficult management

IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Incidence in Canadian children 41,000 children <5 years of age treated in the community each year 9600 hospitalized older children have decreased incidence leading cause of mortality and morbidity amongst Canadian Inuit; outbreak in several communities on Baffin Island (adult and child)

Pathogens CAP generally caused by a single organism Even with extensive diagnostic testing, most investigators cannot identify a specific etiology for CAP in ≥ 50% of patients. In those identified, S. pneumoniae is causative pathogen 60-70% of the time

Pathogens in pediatric CAP Pediatr Infect Dis J :

Pneumococcal pneumonia Most common cause of CAP Gram positive diplococci “ Typical ” symptoms (e.g. malaise, shaking chills, fever, pleuritic hest pain, cough) Lobar infiltrate on CXR Rarely bacteremic in children

Atypical Pneumonia Second most frequent cause (especially in younger population) Commonly associated with milder symptoms: subacute onset, non-productive cough, no focal infiltrate on CXR Mycoplasma: younger Pts, extra-pulmonary symptoms (URI, rash), headache, sore throat Chlamydia pneumoniae: young adults, year round, URI, sore throat

Viral Pneumonia Most common cause in children RSV, influenza, parainfluenza Influenza is the most important viral cause in adults, especially during winter months Post-influenza pneumonia (secondary bacterial infection) S. pneumo, Staph aureus

Other bacteria Staphylococcus aureus Severe disease, prior viral pneumonia Gram negative bacteria Klebsiella – neonates Branhamella catarrhalis - sinus disease, otitis, COPD H. influenzae - Rare Anaerobes Aspiration pneumonia, dental disease

Clinical Features of C. Trachomatis Pneumonia Onset at 3 to 11 wks of age Cough greater than one week in duration Prior conjunctivitis Afebrile tachypnea with diffuse rales Hyperinflation and interstitial infiltrates on chest film Eosinophilia Increased IgM Increased IgA and IgG

Management of CAP: When to obtain a CXR Child < 5 years of age with high fever and high WBC of uncertain source Ambigusous clinical findings Suspected complication, i.e. pleural effusion Pneumonia is prolonged and unresponsive to treatment

Management of CAP: Considerations for admission Child aged less than 6 months of age Toxic appearance Severe respiratory difficulty TcSaO2 < 95% Dehydration, vomiting No response to oral medication Immunocompromised child Social circumstances / poor compliance

IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Management of CAP: Antibiotic therapy Child < 5 years old Presumed bacterial pneumonia Amoxicillin, oral (90 mg/kg/day in 2 doses) Alternative: oral amoxicillin clavulanate (amoxicillin component, 90 mg/kg/day in 2 doses) Presumed atypical pneumonia Azithromycin oral (10 mg/kg on day 1, followed by 5 mg/kg/day once daily on days 2– 5); Alternatives: oral clarithromycin (15 mg/kg/day in 2 doses for 7-14 days) or oral erythromycin (40 mg/kg/day in 4 doses) IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Management of CAP: Antibiotic therapy Child ≥ 5 years old Presumed bacterial pneumonia Oral amoxicillin (90 mg/kg/day in 2 doses to a maximum of 4 g/day); for children with presumed bacterial CAP who do not have clinical, laboratory, or radiographic evidence that distinguishes bacterial CAP from atypical CAP, a macrolide can be added to a b-lactam antibiotic for empiric therapy; alternative: oral amoxicillin clavulanate (amoxicillin component, 90 mg/kg/day in 2 doses to a maximum dose of 4000 mg/day, eg, one 2000-mg tablet twice daily) IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Management of CAP: Antibiotic therapy Child ≥ 5 years old Presumed atypical pneumonia Oral azithromycin (10 mg/kg on day 1, followed by 5 mg/kg/day once daily on days 2– 5 to a maximum of 500 mg on day 1, followed by 250 mg on days 2–5); alternatives: oral clarithromycin (15 mg/kg/day in 2 doses to a maximum of 1 g/day); erythromycin, doxycycline for children >7 years old IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Management of CAP: Antibiotic therapy Inpatient (All ages) Presumed bacterial pneumonia Ampicillin or penicillin G; alternatives: ceftriaxone or cefotaxime; addition of vancomycin or clindamycin for suspected CA-MRSA IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Management of CAP: Antibiotic therapy Inpatient (All ages) Presumed atypical pneumonia Azithromycin (in addition to ß-lactam, if diagnosis of atypical pneumonia is in doubt); alternatives: clarithromycin or erythromycin; doxycycline for children >7 years old; levofloxacin for children who have reached growth maturity, or who cannot tolerate macrolides IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Management of CAP: Antibiotic therapy Not completely immunized Presumed bacterial pneumonia: Ceftriaxone or cefotaxime; addition of vancomycin or clindamycin for suspected CA- MRSA; alternative: levofloxacin; addition of vancomycin or clindamycin for suspected CA- MRSA IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Management of CAP: Antibiotic therapy Not completely immunized Presumed atypical pneumonia Azithromycin (in addition to ß-lactam, if diagnosis in doubt); alternatives: clarithromycin or erythromycin; doxycycline for children >7 years old; levofloxacin for children who have reached growth maturity or who cannot tolerate macrolides IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Management of CAP: Antibiotic therapy Mild case or step-down therapy Preferred: amoxicillin (90 mg/kg/day in 2 doses or 45 mg/kg/day in 3 doses); Alternatives: second- or third-generation cephalosporin (cefpodoxime, cefuroxime, cefprozil); oral levofloxacin, if susceptible (16– 20 mg/kg/day in 2 doses for children 6 months to 5 years old and 8–10 mg/kg/day once daily for children 5 to 16 years old; maximum daily dose, 750 mg) or oral linezolid (30 mg/kg/day in 3 doses for children <12 years old and 20 mg/kg/day in 2 doses for children ≥12 years old) IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Management of CAP: Antibiotic therapy Parenteral therapy Preferred: ampicillin (150–200 mg/kg/day every 6 hours) or penicillin ( – U/kg/day every 4–6 h); Alternatives: ceftriaxone (50–100 mg/kg/day every 12–24 hours) (preferred for parenteral outpatient therapy) or cefotaxime (150 mg/kg/day every 8 hours); may also be effective: clindamycin (40 mg/kg/day every 6–8 hours) or vancomycin (40– 60 mg/kg/day every 6–8 hours) IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Management of CAP: Antibiotic therapy Highly resistant S.pneumoniae Parenteral therapy Preferred: ceftriaxone (100 mg/kg/day every 12– 24 hours); Alternatives: ampicillin (300–400 mg/kg/day every 6 hours), levofloxacin (16–20 mg/kg/day every 12 hours for children 6 months to 5 years old and 8–10 mg/kg/day once daily for children 5–16 years old; maximum daily dose, 750 mg), or linezolid (30 mg/kg/day every 8 hours for children <12 years old and 20 mg/kg/day every 12 hours for children ≥12 years old); may also be effective: clindamycin (40 mg/kg/day every 6–8 hours) or vancomycin (40– 60 mg/kg/day every 6–8 hours) IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Management of CAP: Antibiotic therapy Highly resistant S.pneumoniae Oral therapy Preferred: oral levofloxacin (16–20 mg/kg/day in 2 doses for children 6 months to 5 years and 8–10 mg/kg/day once daily for children 5–16 years, maximum daily dose, 750 mg), if susceptible, or oral linezolid (30 mg/kg/day in 3 doses for children <12 years and 20 mg/kg/day in 2 doses for children ≥12 years); Alternative: oral clindamycin (30–40 mg/kg/day in 3 doses) IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Levofloxacin (Levaquin™) Wide-spectrum fluoroquinolone: S pneumoniae, Haemophilus influenzae (nontypeable), Moraxella catarrhalis M pneumoniae, C pneumoniae, Legionella M. tuberculosis Excellent bioavailability: 100% absorbed Well tolerated by children 5-year safety study reported Many interactions Medications: anticoagulants Natural products

Linezolid (Zyvox™) Narrow-spectrum oxazolidinone: Gram+ S pneumoniae, S. aureus, MRSA VRE Excellent bioavailability: ≈100% absorbed Well tolerated for short courses of therapy Headache, diarrhea, nausea Long-term use: Bone marrow suppression, thrombocytopenia > 2 weeks: neuropathy, lactic acidosis, mitochondrial toxicity

Management of CAP: Antibiotic therapy Group A Streptococcus Parenteral therapy Preferred: intravenous penicillin ( – U/kg/day every 4–6 hours) or ampicillin (200 mg/kg/day every 6 hours); Alternatives: ceftriaxone (50–100 mg/kg/day every 12–24 hours) or cefotaxime (150 mg/kg/day every 8 hours); may also be effective: clindamycin, if susceptible (40 mg/kg/day every 6–8 hours) or vancomycin (40–60 mg/kg/day every 6–8 hours) IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Management of CAP: Antibiotic therapy Group A Streptococcus Oral therapy Preferred: amoxicillin (50–75 mg/kg/day in 2 doses), or penicillin V (50–75 mg/kg/day in 3 or 4 doses); Alternative: oral clindamycin (40 mg/kg/day in 3 doses) IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Management of CAP: Antibiotic therapy Mycoplasma pneumoniae Parenteral therapy Preferred: intravenous azithromycin (10 mg/kg on days 1 and 2 of therapy; transition to oral therapy if possible); Alternatives: intravenous erythromycin lactobionate (20 mg/kg/day every 6 hours) or levofloxacin (16-20 mg/kg/day every 12 hours; maximum daily dose, 750 mg) IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Management of CAP: Antibiotic therapy Mycoplasma pneumoniae Oral therapy Preferred: azithromycin (10 mg/kg on day 1, followed by 5 mg/kg/day once daily on days 2–5); Alternatives: clarithromycin (15 mg/kg/day in 2 doses) or oral erythromycin (40 mg/kg/day in 4 doses); for children >7 years old, doxycycline (2–4 mg/kg/day in 2 doses; for adolescents with skeletal maturity, levofloxacin (500 mg once daily) or moxifloxacin (400 mg once daily) IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

François Boucher MD, FRCPC Pneumonia caused by MRSA

CA-MRSA: Antibiotic susceptibility Unlike HA-MRSA, usually susceptible to antibiotics other than vancomycin Typically also susceptible to Clindamycin (!inducible resistance!) TMP/SMX Gentamicin Erythromycin Fluoroquinolones Barton M et al. Can J Infect Dis Med Microbiol 2006; 17(Suppl C): 1B-24B

CA-MRSA risk factors Children less than 2 years old Minority populations: Native or Aboriginal African-American Athletes (mainly contact-sport participants) Injection drug users Men who have sex with men Military personnel Inmates of correctional facilities Veterinarians, pet owners and pig farmers Barton M et al. Can J Infect Dis Med Microbiol 2006; 17(Suppl C): 1B-24B

MRSA pneumonia in children: When to suspect… For children hospitalized with severe CAP empiric therapy for MRSA is recommended (pending sputum and/or blood culture results): Those requiring an intensive care unit (ICU) admission, OR Necrotizing or cavitary infiltrates, OR Empyema Lui C, et al. Clin Infect Dis. 2011;52:1-38

Management of CAP: Antibiotic therapy MRSA susceptible to clindamycin Parenteral therapy Preferred: vancomycin (40–60 mg/kg/day every 6–8 hours or dosing to achieve an AUC/MIC ratio of >400) or clindamycin (40 mg/kg/day every 6–8 hours); Alternatives: linezolid (30 mg/kg/day every 8 hours for children,12 years old and 20 mg/kg/day every 12 hours for children $12 years old) IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Management of CAP: Antibiotic therapy MRSA susceptible to clindamycin Oral therapy Preferred: oral clindamycin (30–40 mg/kg/day in 3 or 4 doses); Alternatives: oral linezolid (30 mg/kg/day in 3 doses for children >12 years and 20 mg/kg/day in 2 doses for children ≥12 years) IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Management of CAP: Antibiotic therapy MRSA resistant to clindamycin Parenteral therapy Preferred: vancomycin (40–60 mg/kg/day every 6-8 hours or dosing to achieve an AUC/MIC ratio of >400); Alternatives: linezolid (30 mg/kg/day every 8 hours for children <12 years old and 20 mg/kg/day every 12 hours for children ≥12 years old) IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Management of CAP: Antibiotic therapy MRSA resistant to clindamycin Oral therapy Preferred: oral linezolid (30 mg/kg/day in 3 doses for children <12 years and 20 mg/kg/day in 2 doses for children ≥12 years old); Alternatives: none; entire treatment course with parenteral therapy may be required IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

MRSA pneumonia in children Vancomycin Dosing in Children Vancomycin 15 mg/kg/dose every 6 h (60 mg/kg/day) is recommended for serious or invasive disease (data are limited to guide vancomycin dosing in children). Trough concentrations of 15–20 mcg/mL should be considered in those with serious infections, such as bacteremia, infective endocarditis, osteomyelitis, meningitis, pneumonia, and severe SSTI (eg, necrotizing fasciitis) The efficacy and safety of this dose requires additional study Lui C, et al. Clin Infect Dis. 2011;52:1-38

MRSA pneumonia in children Adjunctive therapy for MRSA Not routinely recommended: Protein synthesis inhibitors (eg, clindamycin and linezolid) and intravenous immunoglobulin (IVIG) Some experts may consider these agents in selected scenarios (eg, necrotizing pneumonia or severe sepsis) Lui C, et al. Clin Infect Dis. 2011;52:1-38

Management of CAP: Antibiotic therapy for other etiologic agents The guideline offers specific therapy recommendations for pediatric CAP caused by MSSA… H. influenzae, typable or not Chlamydia & Chlamydophila IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Empyema

Empyema: definition Empyema is inflammatory fluid and debris in the pleural space. It results from an untreated pleural- space infection that progresses from free-flowing pleural fluid to a complex collection in the pleural space.

Pathophysiology Exudative stage Fibrinolytic stage Organization stage

Epidemiology Increase in incidence since the mid-nineties (USA) Particularly among certain age groups

Gupta R. Crowley S. Thorax 2006; 61:

Finlay C et al. Can Respir J 2008

Variables associated with parapneumonic effusions Pneumococcal serotype? NO Age ≥ 3 years (p<0,0001)* Varicella (p<0,0001)* Fever ≥ 7 days (p<0,0001)* Medication use: Ibuprofen (p<0,0001)* Ceftriaxone (p<0,0001)* *: Multivariate regression analysis

Parapneumonic effusions management Small effusions Size of effusion: Small: <10 mm on lateral decubitus radiograph or opacifies less than one- fourth of hemithorax Bacteriology: Bacterial culture and Gram stain results unknown or negative Risk of poor outcome: Low Tube drainage: No; sampling of pleural fluid is not routinely required IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Parapneumonic effusions management Moderate effusions Size of effusion: Moderate: >10 mm rim of fluid but opacifies less than half of the hemithorax Bacteriology: Bacterial culture and/or Gram stain results negative or positive (empyema) Risk of poor outcome: Low to moderate Tube drainage: No, if the patient has no respiratory compromise and the pleural fluid is not consistent with empyema; Yes, if the patient has respiratory compromise or if pleural fluid is consistent with empyema IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Parapneumonic effusions management Large effusions Size of effusion: Large: opacifies more than half of the hemithorax Bacteriology: Bacterial culture and/or Gram stain results positive (empyema) Risk of poor outcome: High Tube drainage: Yes, in most cases IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Parapneumonic effusions management Antibiotic therapy In the case of culture-negative parapneumonic effusions, antibiotic selection should be based on the treatment recommendations for patients hospitalized with CAP The duration of antibiotic treatment depends on the adequacy of drainage and on the clinical response demonstrated for each patient. In most children, antibiotic treatment for 2–4 weeks is adequate IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25

Merci! François Boucher MD, FRCPC